Oligonucleotide specific uptake of nanoconjugates

Abstract

Disclosed are nanoparticles functionalized with an oligonucleotide and a domain, wherein the domain increases cellular uptake of the nanoparticles. The domain is a sequence of nucleobases or phosphate groups, such as a poly thymidine (polyT) sequence or a phosphate polymer (C3 residue) and may be located 5′ to the oligonucleotide 3′ to the oligonucleotide, within, or colinear with the oligonucleotide. Usage of the nanoparticles including modulating gene regulation is contemplated.

What is claimed is: 
     
         1 . A nanoparticle functionalized with an oligonucleotide and a domain, the nanoparticle having the property of being taken up by a cell at an efficiency different than a nanoparticle functionalized with the same oligonucleotide but lacking the domain. 
     
     
         2 . The nanoparticle of  claim 1  wherein the domain is located 5′ to the oligonucleotide. 
     
     
         3 . The nanoparticle of  claim 1  wherein the domain is located 3′ to the oligonucleotide. 
     
     
         4 . The nanoparticle of  claim 1  wherein the domain is located at an internal region within the oligonucleotide. 
     
     
         5 . The nanoparticle of any of the preceding claims wherein the domain is colinear with the oligonucleotide. 
     
     
         6 . The nanoparticle of  claim 1  functionalized with a second oligonucleotide and the domain is associated with the second oligonucleotide. 
     
     
         7 . The nanoparticle of any of the preceding claims wherein the domain comprises a polythymidine (polyT) sequence comprising more than one thymidine residue. 
     
     
         8 . The nanoparticle of any of the preceding claims wherein the domain comprises a polythymidine (polyT) sequence comprising two thymidine residues. 
     
     
         9 . The nanoparticle of any of the preceding claims wherein the domain comprises a polythymidine (polyT) sequence comprising two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty thymidine residues. 
     
     
         10 . The nanoparticle of any one of  claims 1  through  6  wherein the domain comprises a phosphate polymer (C3 residue). 
     
     
         11 . The nanoparticle of any one of  claims 1  through  6  wherein the domain comprises two or more phosphate polymers (C3 residues). 
     
     
         12 . A method of modulating cellular uptake capacity of an oligonucleotide-functionalized nanoparticle comprising the step of:
 modifying the nanoparticle to further comprise a domain that modulates cellular uptake of the oligonucleotide-functionalized nanoparticle compared to the oligonucleotide-functionalized nanoparticle lacking the domain.   
     
     
         13 . The method of  claim 12  wherein the domain increases cellular uptake of the functionalized nanoparticle. 
     
     
         14 . The method of  claims 12  or  13  wherein the domain comprises a polyT sequence comprising more than one thymidine residue. 
     
     
         15 . The method of any one of  claims 12  through  14  wherein the domain comprises a polyT sequence comprising two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty thymidine residues. 
     
     
         16 . The method of any one of  claims 12  through  15  wherein an increase in thymidine residues in the polyT sequence of the first oligonucleotide-functionalized nanoparticle increases cellular uptake compared to the second oligonucleotide-functionalized nanoparticle that does not contain the polyT sequence. 
     
     
         17 . The method of any one of  claims 12  through  16  wherein the domain decreases cellular uptake of the oligonucleotide-functionalized nanoparticle. 
     
     
         18 . The method of  claim 12  wherein the domain comprises a phosphate polymer (C3 residue). 
     
     
         19 . The method of  claim 18  wherein an increase in C3 residues on the first oligonucleotide-functionalized nanoparticle decreases cellular uptake compared to the second oligonucleotide-functionalized nanoparticle that does not contain a C3 residue. 
     
     
         20 . The method of any one of  claims 12  through  19  wherein the oligonucleotide-functionalized nanoparticle is the nanoparticle of any one of  claims 1  through  11 .